| Irisin Attenuates Apoptosis Following Ischemia-Reper fusion Injury Through Improved Mitochondria Dynamics and ROS Suppression Mediated Through the PI3K/Akt/mTOR Axis | |
| Liu, Ji-fei1; Su, Gang2; Chen, Li-xia1; Zhou, Juan-ping1; Gao, Juan1; Zhang, Jia-jia1; Wu, Qiong-hui1; Chen, Wei1; Chen, De-yi1; Zhang, Zhen-chang1 | |
| 2023-08 | |
| Online publication date | 2023-04 |
| Source Publication | MOLECULAR NEUROBIOLOGY Impact Factor & Quartile |
| ISSN | 0893-7648 |
| Volume | 60Issue:8Pages:4261-4272 |
| page numbers | 12 |
| Abstract | Irisin is a muscle-derived hormone that promotes the survival of motor neurons and enhances muscle size following injury. In this study, we investigated the beneficial effects and mechanism(s) of action of irisin in response to cerebral ischemiareperfusion injury (CIRI). Right-middle cerebral artery occlusion (MCAO) and hypoxia/reoxygenation (H/R) models were generated in C57BL/6 J mice. Mouse neuronal cell lines (NSC-34) were used to confirm the molecular mechanisms of the protection afforded by irisin in response to CIRI. We found that irisin (250 mu g/kg) improved cerebral function and reduced the cerebral infarct volume following CIRI. Irisin also protected neuronal cells against ischemia-reperfusion (I/R) induced apoptosis, assessed via TUNEL, and cleaved Caspase-3 staining. Western blotting of neuronal tissue from irisin treated I/R mice showed lower expression of pro-apoptotic Bax and caspase-9 (P < 0.001 and P < 0.01) and increased levels of the pro-survival protein Bcl-2 (P < 0.01 & P < 0.001 vs. I/R). Irisin also reduced the levels of reactive oxygen species (ROS) characterized through malondialdehyde (MDA) assays. Irisin was found to maintain mitochondrial homeostasis through the suppression of mitochondrial fission-linked dynamin-related protein 1 in CIRI mice (P < 0.01 and P < 0.05 v. I/R cohort). Moreover, mitochondrial fusion-related protein (Mfn2) and Opa1 expression were rescued following irisin treatment (P < 0.001 and P < 0.01 v. I/R cohort). Cell-based assays showed that irisin activates PI3K/AKT/mTOR signaling in the neurons of CIRI mice. Furthermore, the beneficial effects of irisin on NSC-34 cell-survival, mitochondrial function, and ROS generation were reversed by VS-5584, a highly specific PI3K/AKT/mTOR inhibitor. Collectively, these data highlight the ability of irisin to alleviate CIRI in vivo and in vitro. The mechanisms of action of irisin include the attenuation of apoptosis through the prevention of mitochondrial fission and increased mitochondrial fusion and the alleviation of oxidative stress through activation of the PI3K/AKT/mTOR axis. We therefore identify irisin as a much- needed therapeutic for CIRI. |
| Keyword | Cerebral ischemia reperfusion injury Mitochondria Reactive oxygen species PI3K AKT mTOR Apoptosis |
| Publisher | SPRINGER |
| DOI | 10.1007/s12035-023-03336-5 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Neurosciences & Neurology |
| WOS Subject | Neurosciences |
| WOS ID | WOS:000972187600002 |
| Original Document Type | Article |
| PMID | 37060502 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/530191 |
| Collection | 兰州大学 |
| Corresponding Author | Zhang, Zhen-chang |
| Affiliation | 1.Lanzhou Univ, Dept Neurol, Hosp 2, 82 Cuiyingmen, Lanzhou 730030, Gansu, Peoples R China; 2.Lanzhou Univ, Inst Genet, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China |
| Recommended Citation GB/T 7714 | Liu, Ji-fei,Su, Gang,Chen, Li-xia,et al. Irisin Attenuates Apoptosis Following Ischemia-Reper fusion Injury Through Improved Mitochondria Dynamics and ROS Suppression Mediated Through the PI3K/Akt/mTOR Axis[J]. MOLECULAR NEUROBIOLOGY,2023,60(8):4261-4272. |
| APA | Liu, Ji-fei.,Su, Gang.,Chen, Li-xia.,Zhou, Juan-ping.,Gao, Juan.,...&Zhang, Zhen-chang.(2023).Irisin Attenuates Apoptosis Following Ischemia-Reper fusion Injury Through Improved Mitochondria Dynamics and ROS Suppression Mediated Through the PI3K/Akt/mTOR Axis.MOLECULAR NEUROBIOLOGY,60(8),4261-4272. |
| MLA | Liu, Ji-fei,et al."Irisin Attenuates Apoptosis Following Ischemia-Reper fusion Injury Through Improved Mitochondria Dynamics and ROS Suppression Mediated Through the PI3K/Akt/mTOR Axis".MOLECULAR NEUROBIOLOGY 60.8(2023):4261-4272. |
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